Document 0103
 DOCN  M95A0103
 TI    Drug resistance and heterogeneous long-term virologic responses of human
       immunodeficiency virus type 1-infected subjects to zidovudine and
       didanosine combination therapy. The AIDS Clinical Trials Group 143
       Virology Team.
 DT    9510
 AU    Shafer RW; Iversen AK; Winters MA; Aguiniga E; Katzenstein DA; Merigan
       TC; Center for AIDS Research, Stanford University Medical Center, CA;
       94305, USA.
 SO    J Infect Dis. 1995 Jul;172(1):70-8. Unique Identifier : AIDSLINE
       MED/95318561
 AB    Plasma human immunodeficiency virus (HIV) type 1 RNA levels, CD4
       lymphocyte changes, and drug resistance were studied in HIV-infected
       patients with 200-500 CD4 lymphocytes/microL who received zidovudine and
       didanosine combination therapy for 2 years. Among 35 patients, 10 had
       sustained and 16 had transient > 10-fold reductions in HIV RNA: 9 did
       not have 10-fold HIV RNA reductions. Only patients with sustained HIV
       suppression maintained increased CD4 cell counts for 2 years (370 to 501
       cells/microL; P = .006). Patients with transient HIV suppression were
       more likely to develop drug-resistant HIV strains (12/16 vs. 5/19, P =
       .01) and reverse transcriptase (RT) mutations (4.5 vs. 2.5/strain; P =
       .02) than were patients with sustained or no HIV suppression. Zidovudine
       resistance occurred with RT mutations at codons 41, 67, 70, 215, and
       219. Multidrug resistance occurred with mutations at codons 62, 75, 77,
       116, and 151. Mutations occurred at codons 60, 68, 118, 210, and 228 in
       > or = 4 patients each. Heterogeneity exists among individual virologic
       responses to zidovudine and didanosine combination therapy. HIV
       resistance mechanisms during combination therapy appear more complex
       than reported with monotherapy.
 DE    Amino Acid Sequence  Base Sequence  Codon  CD4 Lymphocyte Count
       CD4-Positive T-Lymphocytes/IMMUNOLOGY  Didanosine/*THERAPEUTIC USE  Drug
       Resistance, Microbial  Drug Resistance, Multiple  Drug Therapy,
       Combination  DNA Primers  Human  HIV Infections/BLOOD/*DRUG
       THERAPY/IMMUNOLOGY  HIV-1/DRUG EFFECTS/GENETICS/*ISOLATION & PURIF
       Molecular Sequence Data  Point Mutation  Polymerase Chain
       Reaction/METHODS  Reverse Transcriptase/GENETICS  RNA,
       Viral/*BLOOD/ISOLATION & PURIF  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Zidovudine/*THERAPEUTIC USE  CLINICAL TRIAL  JOURNAL
       ARTICLE

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